Immune regulation by dead intestinal epithelial cells
| Project/Area Number |
17H04052
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
ASANO Kenichi 東京薬科大学, 生命科学部, 准教授 (10513400)
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| Co-Investigator(Kenkyū-buntansha) |
濱田 理人 筑波大学, 医学医療系, 助教 (20567630)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
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| Keywords | CCL8 / 炎症性腸疾患 / 死細胞 / DAMPs / マクロファージ / ビメンチン / hnRNP / 腸管免疫 / 細胞死 / CD169 / 大腸炎 / 腸炎 / 炎症 |
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| Outline of Final Research Achievements |
We found that tBHP-treated adult mouse small intestinal epithelial cell (aMos7)-derived conditioned medium (CM) enhances CCL8 production by macrophages that were stimulated in vitro with LPS. The CM alone did not induce CCL8 production by macrophages. These findings suggest that a dead cell-derived factor and bacterial components coordinately promote intestinal inflammation. To identify this dead cell-derived molecule, we fractioned CM from tBHP-treated aMos7 cells by HPLC on sizing column monitored with an ultraviolet spectrum detector. A fraction (approximately 1,000 kDa) that showed CCL8 enhancing activity were further separated by HPLC with a reverse phase (C18) column. Mass spectrometry identified Vimentin and hnRNPa1b2-derived peptides that are known as potential endogenous adjuvants. Role of these molecules in the induction of CCL8 by macrophages will be examined by generating Vimentin- or hnRNPa2b1-knock-down aMos7 cells by CRISPR/Cas9 method.
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| Academic Significance and Societal Importance of the Research Achievements |
近年わが国で炎症性腸疾患の罹患者数が急増しており、新たな治療標的の発見が望まれている。以前に我々は、腸管のCD169マクロファージがCCL8を産生し、腸炎進展に関与することを発見した。抗CCL8抗体はマウスの大腸炎を抑制したことから、マクロファージによるCCL8産生の制御が、炎症性腸疾患の治療戦略策定に寄与すると考え、CCL8産生を促進するシグナル分子同定を目指した。本研究では、腸上皮死細胞から産生される内因性アジュバントが、マクロファージによるCCL8産生を促進することを証明した。今後、これらの分子を同定することで、炎症性腸疾患の急性増悪機序の理解や、治療法開発に役立つことが期待される。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] MT1-MMP recruits the ER-Golgi SNARE Bet1 for efficient MT1-MMP transport to the plasma membrane.2019
Author(s)
Miyagawa, T.,* Hasegawa, K.,* Aoki, Y.,* Watanabe, T.,* Otagiri, Y., Arasaki, K., Wakana, Y., Asano, K., Tanaka, M., Yamaguchi, H., Tagaya, M. and Inoue, H. (*, These authors contributed equally to this work.)
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Journal Title
J. Cell Biol.
Volume: 218
Issue: 10
Pages: 3355-3371
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Generation of and characterization of anti-IL-11 antibodies using newly established Il11-deficient mice.2018
Author(s)
Deguchi Y, Nishina T, Asano K, Ohmuraya M, Nakagawa Y, Nakagata N, Sakuma T, Yamamoto T, Araki K, Mikami T, Tanaka M, Nakano H.
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Journal Title
Biochemical Biophysical Research Communications
Volume: 505
Issue: 2
Pages: 453-459
DOI
Related Report
Peer Reviewed / Open Access
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